Lignin fibers typically influence the mixture performance of stone matrix asphalt (SMA), such as strength, stability, durability, noise level, rutting resistance, fatigue life, and water sensitivity. However, limited studies were conducted to analyze the influence of fibers on the percent voids in mineral aggregate in bituminous mixture (VMA) during the mixture design. This study analyzed the effect of different fibers and fiber contents on the VMA in SMA mixture design. A surface-dry condition method test and Marshall Stability test were applied on the SMA mixture with four different fibers (i.e., flocculent lignin fiber, mineral fiber, polyester fiber, blended fiber). The test results indicated that the bulk specific gravity of SMA mixtures and asphalt saturation decreased with the increasing fiber content, whilst the percent air voids in bituminous mixtures (VV), Marshall Stability and VMA increased. Mineral fiber had the most obvious impact on the bulk specific gravity of bituminous mixtures, while flocculent lignin fiber had a minimal impact. The mixture with mineral fiber and polyester fiber had significant effects on the volumetric properties, and, consequently, exhibited better VMA over the conventional SMA mixture with lignin fiber. Modified fiber content range was also provided, which will widen the utilization of mineral fiber and polyester fiber in the applications of SMA mixtures. The mixture evaluation suggested no statistically significant difference between lignin fiber and polyester fiber on the stability. The mineral fiber required a much larger fiber content to improve the mixture performance than other fibers. Overall, the results can be a reference to guide SMA mixture design.

In this paper, a semi-empirical model of air waves induced by falling rock is described. The model is composed of a uniform motion phase (velocity close to 0 m·s^-1) and an acceleration movement phase. The uniform motion phase was determined based on experimentally and the acceleration movement phase was derived by theoretical analysis. A series of experiments were performed to verify the semi-empirical model and elucidated the law of the uniform motion phase. The acceleration movement phase accounted for a larger portion with a greater height of the falling rock. Experimental results of different falling heights of the goaf showed close agreement with theoretical analysis values. The semi-empirical model could accurately and conveniently estimate the velocity of air wave induced by falling rock. Thus, the semi-empirical model can provide a reference and basis for estimating the speed of air waves and designing protective measures in mines.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

This study addresses the importance of conducting mass movement susceptibility mapping and hazard assessment using quantitative techniques, including machine learning, in the Northern Lima Commonwealth (NLC). Previous exploration of the topographic variables revealed high correlation and multicollinearity among some of them, which led to dimensionality reduction through principal component analysis (PCA). Six susceptibility models were generated using weights of evidence, logistic regression, multilayer perceptron, support vector machine, random forest, and naive Bayes methods to produce quantitative susceptibility maps and assess the hazard associated with two scenarios: the first being an El Niño phenomenon and the second being an earthquake exceeding 8.8Mw. The main findings indicate that machine learning models exhibit excellent predictive performance for the presence and absence of mass movement events, as all models surpassed an AUC value of >0.9, with the random forest model standing out. In terms of hazard levels, in the event of an El Niño phenomenon or an earthquake exceeding 8.8Mw, approximately 40% of the NLC area would be exposed to the highest hazard levels. It also highlights the importance of integrating methodologies to reduce model uncertainty, such as comprehensive analysis of variables supported by high quality data and organized workflows. The findings of this research are expected to serve as a supportive tool for land managers in formulating effective disaster prevention and risk reduction strategies.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

SOC stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal-spatial and vertical distribution characteristics of SOCS on the Western Sichuan Plateau (WSP) using the sparrow search algorithm-random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal-spatial varia-tions in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS on the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed that the SOCS in the study area has increased significantly since 2010, with an increase of 27.88 Tg C compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forest and grassland are the main sources of SOCS, the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total SOC pool in 2020, respectively. Expansion of the wetlands, forest, and grassland areas could increase SOCS in the study area.

Introduction: Cleft lip with or without cleft palate (CL/P) is the most common congenital face anomaly in the world of multifactorial etiology. Objective: To determine the prevalence and characteristics of cleft palate. To identify associated risk factors to guide prevention and/or prenatal detection for early intervention and better health outcomes. To assess the rehabilitation protocols after operations in cleft palate. Design: Retrospective descriptive and clinical study. Patients: One hundred and three children with cleft palate treated in the Department of Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, University of Warmia and Mazury, were included in the study. Methods: Records evaluation was conducted regarding sex, cleft type, mother occupation, parents education, histories of cleft in any of parents. The data were analyzed using R (R core team 2021) and the ordinal logistic regression analyses. Results: Children of stressed mothers during pregnancy had 9.4 times higher odds of having bilateral cleft. While there was no evidence that children sex, order of birth, and body mass as well as risk of maternal toxicity at work or reporting infections or drugs toxicity had a significant effect on the dependent variable. Conclusions: Children of parents with cleft history and having low educated mothers had higher probability of bilateral cleft palate. Children of stressed mothers during pregnancy had higher odds of having bilateral cleft. In literature, there is a lack of reports about rehabilitation in different operations methods in children with cleft palates.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS₂@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS₂ nanosheets, thus constructing hierarchically coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS₂ nanostructures. As a result, the MoS₂@carbon composites, when served as anodes for Li-ion batteries, exhibit a high reversible specific capacity of 820 mAh g^-1, high-rate capability (457 mAh g^-1 at 2 A g^-1), and excellent cycling stability. The superior electrochemical performance makes the MoS₂@carbon composites to be low-cost and promising anode materials for Li-ion batteries.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents.

Source water quality is a key determinant of drinking water quality. The recast European Union 2020/2184 drinking water directive (DWD) introduced the obligation for comprehensive risk assessment in drinking water supplies, including the water source and incorporated new elements of natural origin in the list of parameters to be monitored. The current study is the first comprehensive assessment of 15 natural elements (B, Ba, Be, Ca, Co, K, Li, Mg, Mo, Na, Se, Sr, Ti, U and V) in 1155 (82%) Hungarian drinking water sources, including surface water, bank filtered and groundwater sources. Parameters posing a risk to health (Se, V and U) were typically below the lower limit of quantification (LOQ), but higher concentrations (max. 7.0, 17 and 41 µg/L, respectively) may occur in confined locations, the latter exceeding the DWD parametric value in one water supply. Li in a small geographical area, Mg and Ca in the majority of the water supplies reached the concentration range assumed to be protective to health. Water sources were grouped in 6 clusters based on their element distribution, some of them also showing clear geographical patterns. Water types were not differentiated, with the exception of karstic waters (dominated by Ca and Mg). None of the investigated parameters are expected to be a source of public health concern.

The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system, bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. Creation of new dosage forms for neonatology with the use of software and mathematical technologies in pharmaceutical development allows to create cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a formulation of a new nasal gel formulation with Angiolin using Box-Benken experiment design for the therapy of prenatal CNS damage. It was found that the consistency properties of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component - sodium salt of carboxymethylcellulose. We have optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized composition of the obtained nasal gel has satisfactory parameters of thixotropic properties. The developed 1% gel for neuroprotection with Angiolin meets all the requirements for harmlessness and safety to drug forms of this group - low toxicity, absence of local irritant and allergic effect.

In this paper, based on our previous expertise on ceramic artifacts, several archaeometric methods applied to some samples collected from the Dudești archaeological site (Oltenia region, Romania) are reported for the first time in the literature. The chemical composition and microstructural and morphological characterization of these samples offer important conclusions about the processing conditions. Some specific techniques such as X-ray diffraction (XRD), wave-length-dispersive X-ray fluorescence (WDXRF), Optical microscopy (OM), stereomicroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy, provide composition information about pigments and their decay processes. Additionally, the Brunauer-Emmett-Teller (BET) method helps to estimate pore sizes and specific surface areas. Thermal analysis (TGA) was used to establish details regarding the production technology and the raw materials source used to make the ceramics, too. The obtained results indicated that the ceramics are based on a paste of muscovite, feldspar, with high plasticity, quartz, melanterite, and calcite, the latter in very low concentrations. According to the obtained results, we could assume that non-calcareous clays are present in the investigated samples because calcium exists in low concentrations. Gypsum is present, too, in very low concentration, identified by the presence of sulfate group in WDXRF. In the same context, iron oxides significantly impact the firing atmosphere of iron-rich clay, resulting in blackening under reducing conditions and reddish coloration under oxidative conditions. Using hematite and gypsum as pigments further contributes to the color variations in the pottery. The consistent firing temperature range of 200-600 °C in Dudești pottery implies a standardized production process, the variation in color being dependent on the specific reducing/oxidative regime conditions. This relationship between clay composition and local sources suggests a connection to Neolithic pottery production in the region and their color depending on the reducing/oxidative regime conditions.

Abstract: Short-chain fatty acids (SCFAs) are the major microbial metabolites produced in the gut through the fermentation of non-digestible fibers. SCFAs act through free fatty acid receptor 2 and 3 (FFAR2 and 3), which are known to be expressed on glucagon-like peptide-1 (GLP-1)-secreting L-cells. This pathway is suggested to protect the intestinal mucosa. We aimed to investigate how lack of fiber affects the production of SCFAs and the vulnerability of the co-lon. Additionally, the involvement of FFAR2 and 3 in GLP-1 secretion and intestinal protection. SCFA concentrations in luminal contents from chow- or fiber-free diet-fed mice were analysed by LC‒MS. SCFAs were applied to isolated perfused colons from FFAR2/3 double KO and WT mice, and the secretion of GLP-1 was measured. Dextran sulfate sodium (DSS) colitis was induced in chow- or fiber-free diet-fed mice as well as in FFAR2/3 KO and WT mice. The removal of die-tary fiber significantly decreased total colonic SCFA concentrations, with specific decreases in acetate, propionate, and butyrate. SCFAs significantly increased colonic GLP-1 secretion but not in FFAR2/3 KO mice. In the DSS model, the removal of dietary fiber increased the severity and delayed recovery. Colitis severity was independent of FFAR2 and FFAR3 signaling.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

This article delves into the enduring relevance of Liberal International Relations (IR) Theory amidst persistent criticisms regarding power dynamics and its applicability in emerging states. Despite its detractors, Liberal IR Theory offers a nuanced understanding of state behavior, blending social contexts with power dynamics. It recognizes the intricacies of economic interdependence and advocates for a balanced approach in advancing democracy and human rights. While nationalism poses challenges to international institutions, their adaptability endures. Leaders, albeit constrained, retain the capacity to foster peace through visionary leadership and global cooperation. By acknowledging its limitations and fostering open dialogue, Liberal IR Theory continues to evolve, poised to contribute to a just and peaceful global order.

Soft magnetic composites cores were produced by Spark Plasma Sintering (SPS) from Ni3Fe@ZnFe2O4 and NiFeMo@ZnFe2O4 pseudo-core-shell powders. In the Fe-Ni alloys@ZnFe2O4 pseudo-core-shell composite powders, the core is a large nanocrystalline Permalloy or Supermalloy particle obtained by mechanical alloying, and the shell is a pseudo continuously layer of Zn ferrite particles. The pseudo-core-shell powders have been compacted by SPS at temperatures between 500-700 ºC, with a holding time of 0 minutes. Several techniques were used for the characterisation of the powders and sintered compacts: X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, magnetic hysteresis measurements (DC and AC) and electrical resistivity. The electrical resistivity is stabilised at values of about 7·10-3 Ω·m for sintering temperatures between 600-700 °C and this value is 3 orders of magnitude higher than the electrical resistivity of sintered Fe compacts. The best relative initial permeability was obtained for the Supermalloy/ZnFe2O4 composite compacts sintered at 600 ºC, which decreases linearly for the entire frequency range studied, from around 95 to 50. Up a frequency of 2,000 Hz the power losses are lower than 1.5 W/kg. At the frequency of 10 kHz, the power losses are larger, but they remain at a low level. In the case of Supermalloy/ZnFe2O4 composite compact SPS-ed at 700 °C, the specific power losses are even lower than 5 W/kg. The power losses decomposition proved that intra-particles losses give the main part of the losses.

Geothermal energy, being a clean energy source, has immense potential, and accurate wellbore modeling is crucial for optimizing the drilling process and ensuring safety. This paper presents a novel geothermal wellbore model based on the drift-flux approach, tested under three different temperature and pressure well conditions. The proposed model integrates the conservation equations of mass, momentum, and energy, incorporating the gas-liquid two-phase flow drift-flux model and heat transfer model. Key features include handling heat transfer between the for-mation and the wellbore, addressing the slip relationship between gas and liquid phases, and accounting for wellbore friction. The nonlinear equations are discretized using the finite differ-ence method, and the highly nonlinear system is solved using the Newton-Raphson method. Numerical simulation, validation, and comparison with existing models demonstrate the en-hanced accuracy of this model. In our tests, the model achieved high accuracy in calculating bottom hole pressure and temperature, with Mean Relative Errors (MRE) significantly lower than those of other models. These results offer valuable insights for optimizing drilling parameters and ensuring drilling safety. Comparisons indicate that this approach significantly outperforms others in capturing the complex dynamics of geothermal wellbores, making it a superior tool for geo-thermal energy development.

Nanocellulose (CNC) seems to be a promising surfactant, which, together with expandable graphite (EG), forms the essence of an effective natural-based fire retardant wood coating. In our research, the most suitable composition of the mixture was tested concerning good solubility, dispersion, and consistency. Favorable results were achieved with the formulation composed of a 4% CNC alkaline solution with 80 wt.% of selected EG. Subsequently, six different EG were used to prepare these wood fire retardant coatings. The effectiveness of treatments was verified using a test with a radiant heat source, where the test samples' relative weight loss, relative burning rate, and surface temperature during 600 sec were evaluated. All prepared formulations can be characterized as more or less equally effective. However, the best results were obtained with EG of GG 200 – 100 N, where the mass loss of the sample was 8.10 ± 1.24%. Very good results were also achieved by graphite 25 E + 180 HPH (8.70 ± 0.89%), which is similar to the previous one, even according to the microscopic assessment of the coating as well as the expanded layer. Graphite type 25 K + 180 (8.86 ± 0.65 %) shows the expanded layer's best cohesion, coating uniformity, and ease of application. The results of this work confirmed that the CNC coating itself has significant retardation effects.

The article presents the results of studies aimed to identify the effect of foliar treatments of winter wheat, sugar beets and soybeans with mineral and bioorganic fertilizers. Their positive effect on increasing the concentration of mineral forms of nitrogen in soil was revealed. The crop types have a greater influence on the size of nitrous oxide emissions: in winter wheat crops - 679 µg/m3, soybeans - 637.2 µg/m3, sugar beets - 576.8 µg/m3. The amounts of nitrous oxide emissions were lower in the variants without the use of phosphorus-potassium fertilizers. The Ruter AA fertilizer showed the greatest efficiency on winter wheat crops - 42.7 c/ha. Soybean grain yield of 44.2 c/ha was also achieved by using Ruter AA, as well as Geo-humate together with phosphorus-potassium fertilizers. On the background of the actual supply of phosphorus and potassium, maximum yield was obtained when using N30 on the leaf - 39.3 c/ha. Foliar feeding ensured a yield of sugar beet root crops of up to 67.1-77.4 c/ha on the backdrop of the application of phosphorus-potassium fertilizers with the advantage of using Amino turbo. The largest yield of sugar beet roots without use of mineral phosphorus and potassium was ensured by N30 treatment of the leaf in the phases of 4-6 and 8 leaves - 63.2 t/ha. Of the organo-mineral fertilizers and biostimulants, the best result was shown by the use of Ruter A - 62.6 t/ha. We believe that foliar feeding of crops can be a sustainable farming method that can increase crop yields and reduce N2O emissions.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR-type 2 angiogenesis and vascular morphogenesis as the tyrosin kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between vascular endothelial growth factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and is shared by stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards, and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit set and yield in tree fruit production systems. Here we describe the metagenomics-based detection of plant viruses through bee and pollen samples collected during the spring bloom period from a mixed Prunus and Malus orchard. Twenty-one unique viruses were detected in samples collected during apricot (Prunus armeniaca), sweet cherry (Prunus avium), peach (Prunus persica), and apple blooms. Ilarviruses prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV), Secoviridae family members tomato necrotic ringspot virus, tobacco necrotic ringspot virus, and prunus virus F, and Capillovirus cherry virus A (CVA) were detected in all time points, while other viruses were detected with restricted ranges. These results demonstrate the benefits of area-wide monitoring through bee pollination activities, and provide new insights into the diversity of viruses in tree fruit pollination ecosystems.

We assessed depression, anxiety, and stress in healthcare workers (HCWs) in 2023 and the evo-lution of depression in 2023 compared with 2022. In September-November 2023, 181 HCWs from the Infectious Diseases Hospital, Cluj-Napoca, Romania, completed the Depression, Anxiety, and Stress 21 Scale (DASS-21 R), the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Anxiety Rating Scale (HAM-A). The prevalence of moderate-to-severe levels was 13.81% for DASS-Depression, 18.79% for DASS-Anxiety, 16.02% for DASS-Stress, 19.89% for PHQ-9, and 12.16% for HAM-A. Moderate-to-severe PHQ-9 clinical depression was found in 19.89% of respondents, and moderate-to-severe HAM-A clinical anxiety in 12.16%. Moderate-to-severe PHQ-9 depres-sion was significantly lower in the 2023 study group (19.89%, N=181) compared with 2022 (30.60%, N=114) (p=0.036), also within the 2022-2023 follow-up study group (N=88) (p=0.026). We did not find significant statistical differences between those infected vs. non-infected, vaccinated vs. non-vaccinated, working with vs. non-working with SARS-CoV-2 infected patients. Males were significantly more stressed (p=0.018) and anxious (p=0.034), and physicians in training had the highest prevalence of moderate-to-severe depression (31.60%), followed by physicians (25.64%). In 2023, depression, anxiety, and stress symptoms decreased but remained within a concerning range. By addressing these psychological issues, we can prevent professional crises in the healthcare system.

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care edentulous sites after dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anaesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. Treatment consisted, for the first time to our knowledge, of immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations.

Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Background/Objectives:The first attempts of posterior lumbar interbody fusion can be traced back to the 1940s, where their performance was marked by animosity due to high rates of failure. Nowadays, the use of interbody fusion involves a much more complicated consideration of factors such as global alignment, disc height, fusion rates, and operative risk, all combined at once.Our study aims to examine all these effects using Flarehawk 9 as a means of interbody fusion.Materials and methods: A total of 58 patients underwent open posterior lumbar surgery using Flarehawk 9 between September 2021 and February 2023 with a mean follow up of 1 year.The mean age was 59.8 years old ( range between 33 and 79 years old), 36 of them are males while 22 of them are females. The diagnostic groups included spinal canal stenosis (n=40), failed back surgery syndrome-revision surgery (n=5),spondylolisthesis with slip percentage 25% (n=4),recurrent herniated disc (n=7) and adjacent segment disease (n=2). Results: The majority of patients demonstrated remarkable improvement based on ODI scores.The rate of union varied based on the fused levels and whether the patients had previous surgery or not.The amount of lordosis postoperatively is increased by 2±0.4 degrees.Conclusions: Even though anterior approaches become more and more popular and advanced nowadays, posterior fusion with interbody cage still remains a safe and effective method to treat various spine surgical pathologies with optimal results.

In the drive towards environmental restoration and sustainable energy solutions, effective utilization and management of agricultural crop residues are vital to mitigate greenhouse gas (GHG) emissions and waste accumulation. Converting biogenic wastes into biofuels and bioproducts has the potential to tackle the energy crisis and contribute to environmental remediation. In this investigation, teff husk, primarily generated in Ethiopia during teff production within the agro-industrial sector, is used as the feedstock for the slow pyrolysis process. In Ethiopia, it is estimated that over 1.75 million tons of teff husk are generated annually, with a significant portion being incinerated in the fields, resulting in substantial environmental pollution. This study focuses on assessing teff husk as a potential material for slow pyrolysis, a crucial stage in biochar production, to tap into its biochar-producing potential. To determine the composition of the biomass, the teff-husk was initially analyzed by thermogravimetry. The significant presence of fixed carbon indicates that teff husk is a viable candidate for pyrolytic conversion into biochar particles. The process of slow pyrolysis took place at three varied temperatures—specifically, at 400, 450, and 500 °C. Process parameters of slow pyrolysis such as reaction time, temperature, and heating rate were enhanced to obtain maximum biochar yields. The highest biochar yield of 43.4 wt% was recorded at optimized reaction time, temperature, and heating rate of 120 min, 400 °C, and 4.2 °C/min, respectively. Furthermore, biochar's physicochemical, SEM-EDX, FTIR, and TGA characterization were performed. The thermal stability and carbon content of biochar were found to rise at higher temperatures. Unlike fuel recovery, the results suggest that teff-husk can be used as a feedstock for biochar production.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

Biodiversity has become an issue of global anxiety over the past decades due to its rapid decline worldwide. Bangladesh as one of the most densely populated countries in the world is no more exception. The country, although, was once very rich in biodiversity, during the last few decades as a consequence of the rapid reduction in forest area, urbanisation, habitat modification, unsustainable natural resources use and collection and overall climate change it has decreased alarmingly. Of late, the government, as a signatory of various regional and international conservation treaties, has taken various initiatives to improve country’s dwindling biodiversity. This paper reviews the present situation of biodiversity in Bangladesh, management trends and major causes of biodiversity loss. A separate statutory body is fundamental to ensure conservation, sustainable use and equitable sharing of benefits arisen from biodiversity in the country.

Despite of being an exceptionally biodiversity rich country, the forest coverage of Bangladesh is declining at an alarming rate. Declaration and management of protected areas in this regard is one of the efforts from government side to tackle the loss of biodiversity. The limited numbers of forest-protected areas (FPA), established to conserve the dwindling forest biodiversity of the country with high pressure on them for timber, non-timber forest products, and fuelwood - makes their management challenging. Moreover, most of the FPAs of the country declared only in the recent decades with very limited infrastructure, manpower and policy support for monitoring and governance. Some people-centred approaches for the management of FPAs and alternative livelihood and income generation subsidies although made available through a few project interventions, their number are still inadequate and performance remains less than satisfactory. This chapter provides a critical review of the FPAs of Bangladesh looking at their role in biodiversity conservation, management challenges, and key lessons from previous management interventions with recommendations for the future. It has been revealed that the FPA system of Bangladesh still poorly represents the diverse forest ecosystems with relatively small forest size and lack of corridors for the movement of wildlife. There are ample opportunities to render co-management of FPAs an effective strategy to minimize the conflicts in FPAs management in the country. It is, however, important to ensure the access of local forest-dependent people to different alternative income generating options that may adequately support their livelihoods.

Network centrality analyses have proven successful in identifying important nodes in diverse host-pathogen interactomes. The current study presents a comprehensive investigation of the human interactome and SARS-CoV-2 host targets. We first constructed a comprehensive human interactome by compiling experimentally validated protein-protein interactions (PPIs) from eight distinct sources. Additionally, we compiled a comprehensive list of 1,449 SARS-CoV-2 host proteins and analyzed their interactions within the human interactome, which identified enriched biological processes and pathways. Seven diverse topological features were employed to reveal the enrichment of SARS-CoV-2 targets in the human interactome, with Load centrality emerging as the most effective metric. Furthermore, a novel approach called CentralityCosDist was employed to predict SARS-CoV-2 targets, which proved effective in expanding the pool of predicted targets. Pathway enrichment analyses further elucidated the functional roles and potential mechanisms associated with predicted targets. Overall, this study provides valuable insights into the complex interplay between SARS-CoV-2 and the host cellular machinery, contributing to a deeper understanding of viral infection and immune response modulation.

Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these maladies can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life, and long-term survival of the patient. Still cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also are vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for detection of health conditions has been liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins), to provide valuable information on individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network, that has gained growing recognition as a rich source of biomarkers of airway infections, pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors, ranging from considerable subjection to air pollution and occupational contaminants, to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase of these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. We therefore highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic maladies, to predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgency for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and limitations faced when dealing with their complex matrices.

The escalating levels of atmospheric carbon dioxide (CO₂) due to anthropogenic activities have raised significant concerns regarding their far-reaching consequences, including potential impacts on human brain function. This study employs Agent-Based Modeling (ABM) and a comprehensive literature review to comprehensively examine the effects of varying atmospheric CO₂ concentrations on human brain activity. Historical and projected CO₂concentration data, along with neuroscientific insights, were integrated into the ABM framework to simulate brain activity responses under different CO₂ scenarios. The simulations revealed that elevated CO₂ levels disrupt neural activity and alter neurotransmitter profiles, indicating potential cognitive consequences. Sensitivity analysis emphasized the importance of accurate parameterization for robust simulations. The findings underscore the urgent need to address global CO₂ emissions to preserve cognitive health. Further research is essential to validate and refine the model, incorporating additional factors for a comprehensive understanding of the cognitive repercussions of rising CO₂ levels, crucial for informed policy-making and public awareness campaigns.

Apoptotic cells possess immunomodulatory effects that can be utilized to treat imbalanced immune conditions. Information on the preclinical safety of such treatment is sparse. In this study, the safety of apoptotic cells (Allocetra-OTS) was assessed in a GLP toxicological study on Sprague Dawley rats. Three doses of Allocetra-OTS or vehicle were administered intravenously (IV) for 3 consecutive days. Animals in the Main study were sacrificed on day 4, while animals from the Recovery groups were kept for 14 or 28 days. Allocetra-OTS was well tolerated, and no adverse effects were observed in body weight, clinical signs, food consumption or ophthalmologic observation. Thus, the No Observed Adverse Effect Level (NOAEL) dose was determined as the highest dose administered. An observed elevation in immune cells was suspected to be due to Allocetra-OTS; similarly to other clinical chemistry parameters, however, it was resolved in the Recovery phases. Splenomegaly and a dose-related Extramedullary Hematopoiesis (EMH) in the red pulp were observed, with no adverse events, and were considered to be a normal and expected reaction following IV administration of cell-based therapies. In conclusion, under the conditions of this study Allocetra-OTS was concluded to be safe, further supporting its potential candidacy for clinical studies

The central nervous system (CNS) controls movements and regulates joint stiffness with muscle coactivation, but until now few studies have examined muscle pairs during running. This study aims to investigate differences in lower limb muscle coactivation during gait at different speeds from walking to running. Nineteen healthy runners walked and ran at speeds ranging from 0.8 km/h to 9.3 km/h. Twelve lower limb muscles' coactivation was calculated using the time-varying multi-muscle coactivation function (TMCf) with global, flexor-extension, and rostro-caudal approaches. Spatiotemporal and kinematic parameters were also measured. We found that TMCf, spatiotemporal and kinematic parameters were significantly affected by gait speed for all approaches. Significant differences were observed in the main parameters of each coactivation approach, and in the spatiotemporal, and kinematic parameters at the transition between walking and running. Positive and negative strong correlations were found between global coactivation parameters and center of mass displacements, as well as some spatiotemporal parameters, regardless of gait speed. Our findings suggest that walking and running have different coactivation patterns and kinematic characteristics, with the whole-limb stiffness exerted more synchronously and stably in running. The coactivation indexes and kinematic parameters could be the result of global coactivation, which is a sensory-control integration process used by the CNS to deal with more demanding and potentially unstable tasks like running.

The importance of radar-based human activity recognition increased significantly over the last two decades in safety and smart surveillance applications due to its superiority towards vision-based sensing in the presence of poor environmental conditions, like illumination, increased radiative heat, occlusion, and fog. An increased public sensitivity for privacy protection, and the progress of cost-effective manufacturing, led to a higher acceptance and distribution. Deep learning approaches proved that the manual feature extraction that relies heavily upon process knowledge can be avoided by its hierarchical, non-descriptive nature. On the other hand, ML techniques based on manual feature extraction provide a robust, yet empirical based approach where the computational effort is comparatively low. This review outlines the basics of classical ML- and DL-based human activity recognition and its advances while taking recent progress of both categories into regard. For every category, state-of-the-art methods are introduced, briefly explained and discussed in terms of their pros, cons and gaps. A comparative study is performed to evaluate the performance and computational effort based on a benchmarking data set to provide a common basis for the assessment of the techniques’ degree of suitability.

This study assesses the impact of incorporating an adaptive learning mechanism into an agent-based model (ABMS) simulating behavior on a university campus during the course of a pandemic outbreak, with a particular case on the COVID-19 pandemic. The aim is to reduce overcrowding and infections on campus through the use of Reinforcement Learning (RL). Our findings indicate that RL is a viable approach for effectively representing agents’ behavior within this context. The results reveal specific temporal patterns of overcrowding violations. While our study successfully mitigated campus crowding, it had limited influence on altering the course of the epidemic. This highlights the necessity for comprehensive epidemic control strategies that consider the role of individual decision-making influenced by adaptive learning, along with the implementation of targeted interventions. This research significantly contributes to our understanding of adaptive learning within complex systems and offers valuable insights for shaping future public health policies in similar community settings. Future research directions encompass exploring various parameter settings and updating representations of the disease’s natural history.

In order to examine the impact of geometric configuration of the human vocal tract on the redistribution of acoustic energy in the frequency spectrum, it is necessary to assemble computation models, which facilitate simple modification of the model’s geometric characteristics. This article describes how the human vocal tract model was constructed using so-called super-elements using the improved reduced system method. The mentioned procedure allows using such a model for demanding optimization calculations, for which the model is modified on the super-element level. Furthermore, the article presents an alternative approach, in which an isoparametric element of a higher degree polynomial was derived. Both approaches were compared and used to find the geometric configuration of the human vocal tract amplifying acoustic energy values on the frequency spectrum to around 3kHz.

There are strong indications that the built environment intertwines consistently with the advent of Covid-19 and the need for post-disaster recovery. The advent of the Covid-19 pandemic has exerted adverse effects on both human and global developments; while the efforts to combat this menace call for an integrated human social capital index. This research seeks to adequately enhance the comprehension of how the built environment can be enhanced through resilience in the backdrop of the Covid-19 pandemic. The study's goal is to investigate the impact of a resilient built environment on increasing resilience in the aftermath of the Covid-19 pandemic in Nigeria. Overall, the quantitative study test the impact of four built environments resilience indices (Built Environment capitals; Disaster management indices, Awareness of the Covid-19 Pandemic, and Built Environment adaptive strategies) on Human social capital and Covid-19 pandemic Indices. This study reveals the role of human social capital in achieving a resilient built environment in the wake of Covid 19 pandemic in Nigeria. Also, built environment capitals, disaster management indices, and awareness on the Covid-19 have indirect effects on Covid-19 pandemic indices through the human social capital. The implication of the study is useful for Post-Covid 19 recovery; which is important for future planning of the built environment in Nigeria.

Perfluorohexane sulfonate (PFHxS) is a widely detected replacement for legacy long-chain perfluoroalkyl substances (PFAS) in the environment and human blood samples. Its potential toxicity led to its recent classification as a global regulated persistent organic pollutant. Although animal studies have shown a positive association between PFHxS levels and hepatic steatosis and hepatocellular hypertrophy, the link with liver toxicity, including end-stage liver cancer, remains inconclusive. In this study, we examined the effects of PFHxS on the proliferation of human hepatocellular carcinoma (HCC) cells, Hep3B and SK-Hep1. Cells were exposed to different PFHxS concentrations for 24–48 hr to assess viability and 12–14 days to measure colony formation. Viability of both cell lines increased at PFHxS concentrations <200 μM, decreased at >400 μM, and were highest at 50 μM. Colony formation increased at <300 μM and decreased at 500 μM PFHxS. Consistent with the effect on HCC proliferation, PFHxS increased expression of proliferating cell nuclear antigen (PCNA) and cell-cycle molecules (CDK2, CDK4, cyclin E, and cyclin D1). In summary, PFHxS exhibited a biphasic effect on HCC cell proliferation, promoting survival and proliferation at lower concentrations and being cytotoxic at higher concentrations. This suggests that PFHxS potentially exacerbates HCC progression.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ dysfunction. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium. In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity in a concentration-dependent manner. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. The results indicate that ERCM from AMSCs containing a large amount of GFs and NFs improve wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production.

The role of mesenchymal-to-endothelial transition in the angiogenic response is controversial. Toward this, the present study aimed to determine if fibroblasts contribute to angiogenesis. Endothelial differentiation of fibroblasts was induced by culturing MRC-5 cells (human fetal lung fibroblast cells) on top of Matrigel hydrogel or embedded inside the hydrogel. The formation of ca-pillary-like networks in response to angiogenic signals was observed. The tube formation occurs quickly and can be visualized us-ing a phase-contrast inverted microscope, and/or the cells can be treated with DAPI before the assay and tubes can be visualized through fluorescence or confocal microscopy. Furthermore, fibroblasts cultured in a higher concentration invaded the Matrigel hydrogel and formed stem-cell-like spheroids. These spheroids embedded in matrigel matrices of varying densities sprouted to form 3D connective-tissue networks. Collectively, our results highlight the endothelial differentiation capacity of human lung fibroblasts. The results obtained in this work may have an impact on the search for alternative cell sources for vascular tissue engineering and the overcome of obstacles to vascularization of autologous tissue-engineered constructs and the production of functional grafts for clinical use.

Quantitative polymerase chain reaction (qPCR) is the gold standard approach for detecting a variety of pathogens either via probe-based or SYBR green detection chemistry. Generally, probe-based detection is more specific than SYBR green chemistry. This report describes work done in using a FAM probe targeting a specific segment of the human KRAS gene for detecting presence and relative abundance of the gene in human gastric CloTest samples. Results indicate ineffective detection of the human KRAS gene in samples that are shown to harbor the gene through a similar qPCR assay using SYBR green detection chemistry. Such observations point to inability of the designed FAM probe to bind to target segment of the human KRAS gene that suggests a region of rapid genomic evolution that require close surveillance in the public health community. Given its rapid genomic evolution, this probe region may be an important region in the human KRAS gene playing critical functional roles in either molecular recognition or other structural functions. Overall, human KRAS gene may be undergoing rapid genomic evolution, and qPCR probes targeting specific segment of the gene may be rendered ineffective in short time clinically, thereby, making SYBR green qPCR assay a more reliable choice.

When following a prescribed route, we need to decide at each intersection which way to proceed. The present work addressed several factors that might influence the difficulty of this decision making process. Participants repeatedly followed a route through a virtual maze with twelve or eighteen intersections, and with two or three choices per intersection. One group performed task S, which promoted decision making by the serial order strategy since all intersections looked alike. Another group performed task SA, which allowed the use of the serial order and the associative cue strategy since unique visual cues were presented at each intersection. We found that in both tasks, participants were more accurate in making decisions on routes with twelve rather than eighteen intersections, and more accurate by a similar amount on routes with two rather than three choices. Reaction time in task SA was reciprocal to accuracy; reaction time in task S was generally lower and route-independent. Accuracy in task SA was similar for participants who experienced smooth transport across intersections and those who experienced abrupt transport, while accuracy in task S was lower for participants who experienced smooth rather than abrupt transport across intersections. We conclude that the number of intersections and the number of choices were equivalent determinants of route following difficulty. We further conclude that optic flow during turns at intersections interfered with anticipatory decision making in task S; hence natural (smooth) transport across intersections did not enhance route following performance.

The development of using mitochondrial transplantation in medical therapy are currently discussed. According to the endosymbiotic theory, the movement of mitochondria between different cells is possible. Therefore, an idea of transferring the mitochondria purified from the cells with a limited lifespan to shorten the lifespan of immortal cancer cells was generated. Human umbilical vein endothelial cell (HUVEC) is a kind of primary cell with a limited lifespan. In the present study, the mitochondria purified from HUVEC were applied to alter the malignance of B16F10 melanoma cell. In the comparison of the basic function of mitochondria, HUVEC mitochondria exhibited a higher mitochondrial membrane potential (MMP), while the lower levels in ATP, mitochondrial DNA (mt-DNA) and mitochondrial protein (mt-protein) as compared to melanoma B16F10. After transplanted the B16F10 with HUVEC mitochondria, the migration, invasion, and the proteins involved in cancer stemness were decreased, however, the proteins involved in cell proliferation, such as cyclin D1 and cyclin E1 were increased. In addition, the levels of ATP, mt-DNA and mt-protein of B16F10 were also reduced. As for the dynamics of mitochondria, the reduced expressions of DRP1 and LC3 II revealed that transferred mitochondria can attenuate the mitophagy of B16F10. In mice, inoculated the B16F10 carrying the transplanted HUVEC mitochondria resulted in the larger size of tumor, which is corresponded to the higher levels of cyclin D1 and E1. Interestingly, the lower expressions of N-cadherin, α-SMA and MMP-9 reveled the tumor were decreased in mesenchymal characteristics. Therefore, despite the HUVEC mitochondria did not inhibit the proliferation of B16F10, the metastatic characteristic was reduced.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

This paper argues that the neoliberal consensus about education finance has broken down due to growing economic inequality. First, I use a comparative historical analysis of political alliances to examine patterns of world trade and nations’ policies for economic and educational development since World War II. The United States emphasized STEM-collegiate preparation for all students, while most countries continued the dual emphasis on technical-tertiary and higher education. Educational policy in the US and Pacific region also shifted to reliance on markets and student loans resulting in worsening economic inequality in access. Nations with dual technical and academic pathways in secondary and postsecondary education systems expand college enrollment rates more rapidly than the US. They also experience class conflict between the working-middle class and the new technology elite. Next, I examine how education policy shifted from national planning aligned with public funding to market-based incentives for institutional development, further exposing gaps in opportunity within nations. Finally, recognizing the variations in systemic causes of inequality, I argue that governments, education agencies, and civic activists can best promote equity by organizing to address barriers to opportunity for groups left behind in the wake of withering neoliberal education policy.

Hippotherapy is a popular rehabilitation method for children with cerebral palsy (CP), which is done by riding an actual horse or a horse riding simulator (HRS) device. Riding a real horse is more expensive than using an HRS device due to its high maintenance cost. However, most HRS devices commonly sold in the market are designed as exercise devices, not rehabilitation devices. Most of them are designed to simulate a horse's walk, trot, canter, or gallop gait at various speeds. Hippotherapy aims to improve the walking ability of CP patients. Therefore, the device should aim to replicate the walking gait of a healthy human, the end goal of hippotherapy. This problem motivates us to design and build a specialized HRS device replicating the walking gait of a healthy human that is suitable for hippotherapy, which is achievable by simulating a horse walking gait with several adjustments. We first studied and observed the walking gait cycle of a horse, then analyzed and derived a formulation of it. We then continue by designing an HRS device using a single electrical rotational motor and mechanical means to replicate the walking gait of a horse, then tune it to an extent to replicate a human walking gait. To measure the performance of our design, we compare the gait of the user when riding our device versus walking.

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies compared to in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

Background: The demand in the development of cancer nanomedicine has increased due to various limitations in conventional cancer therapy. This study assessed the mRNA transcriptomic profiling of human HepG2 cells exposed to C. roseus-AgNPs. Methods: The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with C. roseus‑AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, DEG analysis, GO analysis, and pathway analysis. Results: The mean IC₅₀ values of C. roseus‑AgNPs on HepG2 was 4.38±1.59 µg/mL while on THLE3 cells was 800±1.55 µg/mL. Transciptomic profiling revealed an alteration of 296 genes. C. roseus‑AgNPs induced the expression of stress-associated genes such as MT, HSP and HMOX-1. Cellular signaling pathways were potentially activated through MAPK, TNF and TGF pathways that responsible for apoptosis and cell cycle arrest. The alteration of ARF6, EHD2, FGFR3, RhoA, EEA1, VPS28, VPS25, TSG101 indicated the uptake of C. roseus-AgNPs via both clathrin-dependent and clathrin-independent endocytosis. Conclusions: This study provides the new insights on gene expression study of biosynthesized AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicates the C. roseus‑AgNPs as an ideal anticancer candidate.

Huntington’s disease (HD) is a late-onset; progressive, dominantly inherited neurological disorder marked by an abnormal expansion of polyglutamine (poly Q) repeats in Huntingtin (HTT) protein. The pathological effects of mutant Huntingtin (mHTT) are not restricted to the nervous system but systemic abnormalities including immune dysregulation have been evidenced in clinical and experimental settings of HD. Indeed, mutant huntingtin (mHTT) is ubiquitously expressed and could induce cellular toxicity by directly acting on immune cells. However, it is still unclear if selective expression ofmHTT exon1 in neurons could induce immune responses and hemocyte function. In the present study, we intended to monitor perturbations in the hemocytes population and their physiological functions in Drosophila, caused by pan-neuronal expression of mHTT protein. We found that pan-neuronal expression of mHtt significantly alters crystal cells and plasmatocyte count in larvae and adults with disease progression. Interestingly, plasmatocytes isolated from diseased conditions exhibit a gradual decline in phagocytic activity ex vivo at progressive stages of the disease as compared to age-matched control groups. We also observed an increased production of reactive oxygen species (ROS) in plasmatocytes at advanced stages of the disease. In addition, diseased flies displayed elevated reactive oxygen species (ROS) in circulating plasmatocytes at the larval stage and in sessile plasmatocytes of hematopoietic pockets at of disease. All the parameters were monitored progressively, targeting the circulation at larvae stage and hematopoietic pockets in adults at different disease stages, and many alterations were documented in the early stage itself. These findings strongly implicate that neuronal expression of mHtt alone is sufficient to induce non-cell-autonomous immune dysregulation in vivo. Based on these findings, we propose that further insight into the mechanisms through which neuronal expression of mHtt might be inflicting the innate immune responses would facilitate therapeutic inventions aimed at amelioration of HD pathology and improving the quality of life of the patients.

The paradigm of the Somatic Mutation Theory (SMT) is failing and a new paradigm is in the making but not yet established. What is being challenged is a conceptual approach that involves the entire human biology and the development of chronic diseases. The behavior of breast cancer is well compatible with the concept that the primary tumor is able to control its microscopic metastases, in the same way that an organ (e.g., the liver) is able to control its physiological size. This finding suggested that breast cancer and its metastases may behave as an organoid. The new paradigm under construction considers the origin of tumors as a disturbance in the communication network between tissue cell populations and between cells and extracellular matrix, and supports a systemic approach to the study of both healthy and pathologic tissues. The commentary provides a rationale for the role of physical exercise in the control of tumor dormancy according to a human evolutionary perspective.

The article discusses the issues related to the safety of transport of dangerous goods by road. Research on accidents in transport unambiguously points to the human factor, which is most responsible for causing the accident. Determining the causes of driver unreliability in the hu-man-vehicle-environment system requires thorough research. Unfortunately, in this case, experimental research with human involvement is limited in scope. This leaves modeling and simulation of the behavior of the human factor, i.e., the driver transporting dangerous goods. The human being, due to its complexity, is a challenging element to parameterize. The literature presents various attempts to model human actions. In their work, the authors used heuristic methods, specifically fuzzy set techniques, to build a human factor model. In these models, human actions were specified using a verbal or linguistic description. The specificity of fuzzy sets allows to "naturally" limit the "precision" in describing human behavior. The model was built based on the author's questionnaire and expert research, based on which individual features were selected. Then, the traits were assigned appropriate states. The output parameter of the model is λL - the intensity of human error. The obtained values of the intensity of the accident caused by the driver's error were implemented into the author's method of risk assessment. They constituted one of the factors determining the probability of an accident in the transport of dangerous goods, which allowed to determine the optimal route of transport of these goods characterized by the lowest risk of an undesirable event on the route. The article presents the model's assumptions, structure, and features included in the model, which have the most significant influence on shaping the intensity of human error. The results of the simulation studies showed a diversified effect of the analyzed characteristics on the driver's efficiency.

Memory is probably one of the most complex cognitive functions of the human, and in many years, thousands of studies have helped us to better recognize this brain function. One of the reference textbooks in neuroscience, which has also elaborated on the memory function, is written by Prof. Kandel and his colleagues. In this book, I encountered a number of ambiguities when it was explaining the memory system. Here, I am sharing those points, either to find an answer for them, or to let them be a suggestion for our future works. Prof. Kandel has spent most of his meritorious lifetime on studying the memory system; however, the brain is extremely complex, and as a result, we still have many years to comprehensively understand the neural mechanisms of brain functions.

The main purpose of this research is to analyze the perception of climate change impacts on human health in Bangladesh through data from nationality representative surveys conducted in some district of Bangladesh. In Bangladesh there have a few research has been conducted on public perceptions about the impact of climate change on human health. A structured questionnaire method was conducted, and data collected from 615 respondents. The findings of this study reveal that out of 615 respondents, 76.0% of the respondents replied positively while remaining 24.0%, almost one-fourth of total respondents, indicated that they have not heard the term climate change before. Knowledgeable in climate change, 92.5% of respondents agreed that climate change has an impact on human health while only 7.5% respondents disagreed with this statement. 90.5% of respondents argued that they are agreed with the opinion that climate change is a serious threat to human health.

Changing mobility patterns combined with changes in the climate present challenges and opportunities for global health, requiring effective, relevant and humane policy responses. This study used data from a systematic literature review that examined the intersection between climate change, migration and health. The aim of the present study was to synthesize policy recommendations in the peer-reviewed literature, regarding this type of environmental migration with respect to health, to strengthen the evidence-base. Systematic searches were conducted in four academic databases (PubMed, Ovid Medline, Global Health and Scopus) and Google Scholar for empirical studies published between 1990 – 2020 that used any study design to investigate migration and health in the context of climate change. Studies underwent a two-stage protocol-based screening process and eligible studies were appraised for quality using a standardized mixed-methods tool. From the initial 2,425 hits, 68 articles were appraised for quality and included in the synthesis. Among the policy recommendations, six themes were discernible: (1) avoid the universal promotion of migration as an adaptive response to climate risk; (2) preserve cultural and social ties of mobile populations; (3) enable the participation of migrants in decision-making in sites of relocation and resettlement; (4) strengthen health systems and reduce barriers for migrant access to health care; (5) support and promote optimization of social determinants of migrant health; (6) integrate health into loss and damage assessments related to climate change. The results call for transformative policies that support the health and wellbeing of people engaging in, or affected by mobility responses, including those whose migration decisions and experiences are influenced by climate change, and to establish and develop inclusive migrant healthcare.

Generative models for images, audio, text and other low-dimension data have achieved great success in recent years. Generating artificial human movements can also be useful for many applications, including improvement of data augmentation methods for human gesture recognition. The object of this research is to develop a generative model for skeletal human movement, allowing to control the action type of generated motion while keeping the authenticity of the result and the natural style variability of gesture execution. We propose to use a conditional Deep Convolutional Generative Adversarial Network (DC-GAN) applied to pseudo-images representing skeletal pose sequences using Tree Structure Skeleton Image format. We evaluate our approach on the 3D-skeleton data provided in the large NTU RGB+D public dataset. Our generative model can output qualitatively correct skeletal human movements for any of its 60 action classes. We also quantitatively evaluate the performance of our model by computing Frechet Inception Distances, which shows strong correlation to human judgement. Up to our knowledge, our work is the first successful class-conditioned generative model for human skeletal motions based on pseudo-image representation of skeletal pose sequences.

The sun bear is conservation mammal in Indonesia. The ecological problems as conflict among mammals and human often happen around wildlife, the one of the case is the conflict between sun bear (helarctos malayanus) with human. In Pasaman where around the anthropogenic landscape is bounded by natural forest as sun bear habitat. In this decade, the story has recorded about ±16 incidents. The aim of this research is to geospatial modeling the area of potential conflict between sun bear- human. The method in this research is to use natural logarithmic and regression logistic. The tool is geographical information system and maximum entropy. The result of this research, there has found the distribute energy each variable landscape ecosystem. The statistical model of the potential conflict it has spread on landscape ecosystem. The average value of AUC prediction in this model is at number of 0.91. The variable contribution which affect are forest edge at number of 39.2%, the alternative food (plantation) at number of 31.4%, and forest fragmentation at number of 16.9%.

Daily exposure of skin to environmental stressors leads to molecular and morphological changes ascribed as premature aging. These stressors include solar radiation, industrial pollution, fossil fuel and carbon emissions, which cause cellular damage that induces an inflammatory response in skin. Several inflammatory components are known to be involved in triggering the senescence-associated secretory phenotype (SASP) which is known to accelerate aging. It is hypothesized that preventing induction of inflammation by environmental stressors can prevent premature aging. Since it is known that nicotinamide (Nam) has anti-inflammatory properties, we tested whether Nam can inhibit environmental stressor-induced inflammation. Exposure of keratinocytes to UVB, urban dust, diesel exhaust, and cigarette smoke extract stimulated production of the inflammatory mediators PGE2, IL-6, and IL-8 and induced gene expression patterns associated with apoptosis, DNA repair, and cell cycle control. In all cases, Nam treatment significantly inhibited these stress-induced responses. Nam also reduced IL-8 levels stimulated by the combination of topically applied particulate matter (PM2.5) and UV exposure in 3D skin equivalents. Under 5% 02 conditions that more closely mimic physiological 02 levels, Nam had a heightened inhibitory effect on UVB-induced PGE2 levels in keratinocytes. In a UV-challenge study, treatment with Nam reduced skin surface IL-1RA/IL-1 inflammatory biomarkers and erythema that were induced by solar simulated radiation. These findings provide a body of evidence that Nam can mitigate in part the skin’s inflammatory response elicited by exposure to environmental stressors. This supports the potential that Nam can inhibit premature aging and help maintain skin’s functionality and appearance.

Recently, it was confirmed that ACE2 is the receptor of 2019-nCoV, the pathogen causing the recent outbreak of severe pneumonia in China. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. It remains unclear why it is the lung but not other tissues among which ACE2 highly expressed is mainly infected. We hypothesized that there could be some other genes playing key roles in the entry of 2019-nCoV into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of 2019-nCov than ACE2 (energy score: -15.7 vs. -6.9 [kcal/mol]). Given these observations, we suggest that AGTR2 could be a putative novel gene for the the entry of 2019-nCoV into human cells but need further confirmation by biological experiments. Finally, a number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted.

Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection with adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs that can be identified by embryonic stem cell markers express components of the renin-angiotensin system and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB rarely develops distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the renin-angiotensin system to improve overall symptom-free survival and maintain quality of life.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are environmental pollutants with a great persistence, capacity of bioaccumulation, and well known important toxic effects in humans and animals. Incinerators of hazardous, municipal and medical waste, chlorine bleaching of paper pulp, cement plants, and the traffic of motor vehicles are the most frequent emission sources of these compounds. The diet, followed at a great distance by inhalation, is generally the main way of human exposure to PCDD/Fs. Human biomonitoring is of a great importance to prevent potential adverse effects derived from exposure to chemicals such as PCDD/Fs. In relation to this, blood is among the most used biological monitors. In the current review, we have summarized the recent information (2000-2009) published in the scientific literature (databases: Scopus and PubMed) on the concentrations of PCDD/Fs in blood samples of non-occupationally exposed populations, as well as in some groups of occupationally exposed individuals. We have revised a number of studies conducted in various African American, Asian and European countries, and Australia. Unfortunately, the information is quite limited. No data are available for most countries over the world. Based on the results here reviewed –where available- the current health risks for the general populations do not seem to be of concern. Moreover, taking into account the important reductions observed in the levels of PCDD/Fs in foodstuffs, new decreases in the concentrations of PCDD/Fs in blood -and other biological tissues- are very probable in the immediate years.

Thought runs through the mind like blood runs through our body to keep us alive. Like the mind, the body does not stay inert and is in constant motion. Not a single cell in our body is left inert unless cell is under stress or dying. These scenarios are reflected upon when a person is sick, the person lies in bed with less movement; however, is active when the person is healthy. The topic of mechanical stimulation has emerged due to the increasing understanding of the physical stimulations we face each day. Further understanding of the mechanically-regulated mechanism can help us explore the pathological events in a disease. Here, we reviewed the role of sensory proteins in pathological events that are observed in cardiomyopathy, cancer, respiratory, renal, obesity, genetics, physical injury and bacterial infection. Taken together, sensory proteins are mechanically-activated which assist reception of external physical stimulation and convert into biochemical to trigger intracellular signaling cascade.

The rapid development of algorithms for skeleton detection with relatively inexpensive contactless systems and cameras opens the possibility of virtual exercise therapy for patients with different complications. However, evaluation and confirmation of posture classifications is still needed. The purpose of this study was therefore to find the most accurate algorithm for automatic classification of human exercise movement. A Kinect V2 with 25 joints identification was used to record movements for data analysis. A total of 10 subjects volunteered for this study. Four algorithms were tested for the classification of different postures in Matlab. These were based on: total error of vector lengths, total error of angles, multiplication of these two parameters and simultaneous analysis of the first and second parameters. A base of 13 exercises was then created to test the recognition of postures by the algorithm, and to analyse subject performance. The best results for posture classification was shown by the second algorithm with an accuracy of 94.9%. The average correctness of exercises among the 10 participants was 94.2% (SD1.8%). The algorithms tested in this study therefore proved to be effective and could potentially form the basis for developing a system for remote monitoring of rehabilitation involving exercise.

Biophoton emission has been experimented for decades. The photo-genic origin of biophoton has also been attributed to the oxidative stress or free radical production. However, there are considerable gaps in quantitative understanding of biophoton emission. In this work, I propose an analytical hypothesis for interpreting a few patterns of steady-state biophoton emission of human, including the dependency on age, the diurnal variation, and the geometric asymmetry associated with serious asymmetrical pathological conditions. The hypothesis is based on an alternative form of energy state, termed vivo-nergy, which is associated with only metabolically active organisms that are also under neuronal control. The hypothesis projects a decrease of the vivo-nergy in human during growth beyond puberty. The hypothesis also proposes a modification of the vivo-nergy by the phases of systematic or homeostatic physiology. The hypothesis further postulates that the deviation of the physiology-modified vivo-nergy from the pre-puberty level is deteriorated by acquired organ-specific pathological conditions. A temporal differential change of vivo-nergy is hypothesized to proportionally modulate oxidative stress that functions as the physical source of biophoton emission. The resulted steady-state diffusion of the photon emitted from a photo-genic source in a human geometry simplified as a homogeneous spherical domain is modeled by photon diffusion principles incorporating an extrapolated zero-boundary condition. The age and systematic physiology combined determines the intensity of the centered physiological steady-state photo-genic source. An acquired pathology sets both the intensity and the off-center position of the pathological steady-state photo-genic source. When the age-commemorated, physiology-commanded, and pathology-controlled modifications of the steady-state photo-genetic sources are implemented in the photon diffusion model, the photon fluence rate at the surface of the human-representing spherical domain reveals the patterns on age, the temporal variation corresponding to systematic physiology, and the geometric asymmetry associated with significant asymmetric pathological condition as reported for spontaneous biophoton emission. The hypothesis, as it provides conveniences for quantitative estimation of biophoton emission patterns, will be extended in future works towards interpreting the temporal characteristics of biophoton emission under stimulation.

There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is the major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of genetic diversity of RSV in Australia, nor the factors that shape this diversity. We conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010-2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6-8 x 10^-4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population, and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year, and only limited evidence for multi-year persistence.

The quality of an educational system is reflected not only in the instructive performances of the educational actors, but also in the degree in which it ensures an adequate professional integration. The undergraduate of today, the graduate of tomorrow needs an as accurate as possible information regarding the labour market, which cannot be achieved only by individual means, but also by resorting to carrier counselling services. The motivation of this research is closely connected to the improvement of the level of communication between the two aspects – on the one hand the academic one, by its finite products, and the economic one, on the other hand – and the opportunities that the cooperation between the two aspects might offer: adjusting the demand-supply ratio on the labor market and above all, stopping massive emigration of young graduates of higher education.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

The importance of predicting the exposure to environmental hazards is highlighted by issues like global climate change, public health problems caused by environment stresses, and property damages and depreciations. Several approaches have been used to assess potential exposure and achieve optimal results under various conditions, for example, for different scales, groups of people, or certain points in time. Micro-simulation tools are becoming increasingly important in human exposure assessment, where each person is simulated individually and continuously. This paper describes an agent-based model (ABM) framework that can dynamically simulate human exposure levels, along with their daily activities, in urban areas that are characterized by environmental stresses such as air pollution and heat stress. Within the framework, decision making processes can be included for each individual based on rule-based behavior to achieve goals under changing environmental conditions. The ideas described in this paper are implemented in a free and open source NetLogo platform. A simplified modeling scenario of the ABM framework in Hamburg, Germany, further demonstrates its utility in various urban environments and individual activity patterns, and portability to other models, programs and frameworks. The prototype model can potentially be extended to support environmental incidence management by exploring the daily routines of different groups of citizens and compare the effectiveness of different strategies. Further research is needed to fully develop an operational version of the model.

Manufactured nanoplastic particles (NPs) are indispensable for in vitro and in vivo testing and health risk assessment of this emerging environmental contaminant. High surface area and inherent hydrophobicity of plastic material, makes production of NPs devoid of any contaminants very challenging. In this study we produced nanoprecipitated polyethylene terephthalate (PET) NPs (300 nm hydrodynamic diameter) and characterized presence of ionic surfactant sodium dodecyl sulfate (SDS) by 1H NMR. Relative ratio of NP/surfactant was monitored on the basis of chemical shifts characteristic for PET and SDS. For a wide range of surfactant/NP ratio (1:17 to 1:1.2), measured zeta potential changed from -42.10 to -34.93 mV, but no clear differences were observed in cellular assays performed in protein-rich media on primary human cells. The remaining impurities contributed to the outcome of biological assays applied in protein-free buffers, such as human red blood cells hemolysis. As size, shape, zeta potential and contaminants of NPs may all be relevant parameters for biological effects of NPs, relative quantification of impurities exemplified in our work by application of 1H NMR for PET NPs and ionic surfactant SDS could be a valuable auxiliary method in quality control of manufactured NPs.

To understand the evolution of the human norovirus GII.P6-GII.6 and GII.P7-GII.6 strains, we analyzed both the RdRp region and VP1 gene in globally collected strains using authentic bioinformatics technologies. A common ancestor of the P6- and P7-type RdRp region emerged approximately 50 years ago and a common ancestor of the P6- and P7-type VP1 gene emerged approximately 110 years ago. Subsequently, the RdRp region and VP1 gene evolved. Moreover, the evolutionary rates were significantly faster for the P6-type RdRp region and VP1 gene than the P7-type RdRp region and VP1 genes. Large genetic divergence was observed in the P7-type RdRp region and VP1 gene compared with the P6-type RdRp region and VP1 gene. The phylodynamics of the RdRp region and VP1 gene fluctuated after the year 2000. Positive selection sites in VP1 proteins were located in the antigenicity-related protruding 2 domain, and these sites overlapped with conformational epitopes. These results suggest that the GII.6 VP1 gene and VP1 proteins evolved uniquely due to recombination between the P6- and P7-type RdRp regions in the HuNoV GII.P6-GII.6 and GII.P7-GII.6 virus strains.

Recent studies have been able to detect α-synuclein (αSyn) seeding in formaldehyde-fixed paraffin-embedded (FFPE) tissues from patients with synucleinopathies using seed amplification assays (SAAs), but with relatively low sensitivity due to limited protein extraction efficiency. With the aim of introducing an alternative option to frozen tissues, we developed a streamlined protein extraction protocol for evaluating disease-specific seeding in FFPE human brain. We evaluated the protein extraction efficiency of different tissue preparations, deparaffinizations, and protein extraction buffers using formaldehyde-fixed and FFPE tissue of a single Lewy body disease (LBD) subject. Alternatively, we incorporated heat-induced antigen-retrieval and dissociation using a commercially available kit. Our novel protein extraction protocol has been optimized to work with 10 sections of 4.5-µm-thickness or 2-mm-diameter micro-punch of FFPE tissue that can be used to seed SAAs. We demonstrated that extracted proteins from FFPE still preserve seeding potential and further show disease-specific seeding in LBD and multiple system atrophy. To the best of our knowledge, our study is the first to recapitulate disease-specific αSyn seeding behavior in FFPE human brain, with structural validation. Our findings open new perspectives in re-evaluating archived human brain tissue, extending the disease-specific seeding assays to larger cohorts to facilitate molecular subtyping of synucleinopathies.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

The knowledge of what separates us genetically from our less-evolved relatives is crucial for gaining new biomedical insights about the human-chimpanzee relatedness for the use of appropriate stand-in towards the development of new treatments and diagnostic aids for various ailments. Although the genomes of humans and chimpanzees share 99% similarity, significant differences exist between the two species in their non-coding intronic regions. However, no work has been carried out in the aspects of target prediction concerning the ‘predicted homology’ in their microRNA sequences. Non-coding miRNAs which are post-transcriptional regulators of development, differentiation, growth, and metabolism, harboring the intronic regions may be crucial for expanding the horizons of our understanding. In this study, we proposed to perform the target prediction for the human-chimp miRNA homologs in the PHEX gene of the human X chromosome using various computational tools and databases. We identified a total of 1296 human miRNAs, 46, 957 gene targets, and 30, 563 targets of human and homologous chimp miRNAs respectively. Furthermore, we analysed gene interacting networks to identify the top interacting targets in both the species. Finally, we interpreted the biological importance of top-interacting miRNAs and their targets. The results demonstrated varying levels of multiplicity and cooperativity between the predicted miRNAs and target genes in the two genera. Such miRNAs may be responsible for the dysregulation of gene expression in several signaling pathways.

Purpose: to assess the effect of photobiomodulation (PBM) on human gingival fibroblast proliferation. Methods: The study was conducted using the primary cell cultures of human fibroblasts collected from systemically healthy donors. Three different laser types: Nd:YAG (1064nm), infrared diode laser (980nm) and prototype led laser emitting 405, 450 and 635nm were used to irradiate fibroblasts. Thanks to the patented structure of that laser, it was possible to irradiate fibroblasts with a beam combining two or three wavelengths. The energy density was 3 J/cm², 25 J/cm², 64 J/cm². The viability and proliferation of cells were determined using the MTT test conducted 24, 48 and 72 hours after laser irradiation. Results: The highest percentage of mitochondrial activity (MA=122.1%) was observed in the group irradiated with the 635nm laser, with an energy density of 64 J/cm² after 48 hours. The lowest percentage of MA (94.0%) was observed in the group simultaneously irradiated with three wavelengths (405 + 450 + 635 nm). The use of the 405nm laser at 25 J/cm² gave similar results to the 635 nm laser. Conclusions: The application of the 635nm and 405nm irradiation caused a statistically significant increase in the proliferation of gingival fibroblasts.

We compare the effect on amyloid fibril formation by two homologous proteins from the family of cystatins, human stefin B (stB) and cystatin C (cysC) in presence of 3 polyphenols: curcumin, resveratrol and quercetin and 2 non-phenolic anti-oxidants: vitamin C (VitC) and N-acetyl cystein (NAC). Some of the experimental data have already been presented, here we compare, further discuss and highlight the results. The amyloid fibril formation was followed by ThT fluorescence and transmission electron microscopy. Inhibitory effects on amyloid fibrillation reaction depended on anti-oxidant class and concentration. The fact that different effect of polyphenols was observed with the two cystatins; Cur acted inhibitory on stB but not on cysC fibril formation, could be explained if the 3 polyphenols would not bind to the same binding site in the fibrils core. Other differences are pointed out and discussed. Synergistic effects of VitC and chosen polyphenols on amyloid fibrilllation of human stB have been explored and are reported here for the first time.

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before 12th gestational week (GW) in women at high risk due to a body mass index (BMI)≥25kg/m2, reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI≥25kg/m2 were evaluated between 2015-2018, 246 in standard diet control group (CG) and 489 in MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1%vs31.7%;p=0.037). Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction (relative risk 95% confidence interval) in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92);p=0.019), obesity (0.51 (0.28-0.92),p=0.041), waist circumference (WC)≥89.5cm (0.54 (0.31-0.94);p=0.022) and MetS (0.56 (0.33-0.94);p=0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI)≥25kg/m2, suggesting that its implementation should be routinely recommended from the first GWs.

Succinate is proposed to be a mediator of muscle exercise-induced adaptations. We studied metabolic health and changes of muscle mass in 6-month-old male mice after 12 weeks of feeding regular diet (RD, 13.4 kcal% fat, 66.8 kcal% carbohydrate, 29.8 kcal% protein), high fat diet (HFD, 60 kcal% fat, 20 kcal% carbohydrates, 20 kcal% protein) and ketogenic diet (KD, 80 kcal% fat, &lt;1 kcal% carbohydrates, 20 kcal% protein) with or without 2% succinate supplements (SUS) in drinking water (n=8-12 per group). Functional overloading of the plantaris muscle (PL) was induced in a group of mice by denervation of the gastrocnemius and soleus muscles at week 6 of feeding different diets. HFD induced the greatest (p &lt; 0.001) increase in body and fat mass. HFD and KD lead to significant (p &lt; 0.01) impairment in glucose tolerance compared to RD. SUS blunted (p &lt; 0.01) initial surge in energy intake when mice were switched from RD to HFD, but did not influence any measures of metabolic health after 12 weeks of the study. Functional overloading lead to ~25% increase in PL mass which was not affected by diet or SUS. In conclusion, SUS does not have a long-term effect on metabolic health or muscle mass.

The West Pomeranian Anti-Crisis Package was an effective tool of the Voivodeship Executive Board of West Pomeranian self-government, which was used to combat and counteract and counteract the social and economic effects of the COVID-19 pandemic. The Anti-Crisis Package was prepared with a view to undertaking systemic, but also point-based measures in order to save and protect regional health care, entrepreneurs, the labour market, but also to use the existing social capital of non-governmental organizations involved in measures reducing the effects of the COVID-19 pandemic. The West Pomeranian Anti-Crisis Package, as evidenced not only by the financial outlays incurred, but also by the outcome of implementing measures achieved in 2020 and their continuation in 2021.

Caveolin is a structural protein within caveolae, which may be involved in transmembrane molecular transport and/or various intercellular interactions within cells. Specific mutations of caveolin-3 in muscle cells are well-known to cause a limb-girdle muscular dystrophy. Altered expression of the caveolin-3 has been also detected in Duchenne's muscular dystrophy, which may be a part of the pathological process leading to muscle weakness. Interestingly, it has been shown that the renovation of nitric oxide synthase (NOS) to the sarcolemma with muscular dystrophy could improve the muscle health, suggesting that NOS may be involved in the pathology of muscular dystrophy. Here, we summarize the notable function of caveolin and/or NOS in skeletal muscle cells, and would like to discuss about their involvement in the pathology as well as possible tactics for the innovative treatment of muscular dystrophies.

Underwater imaging presents unique challenges, notably color distortions and reduced contrast due to light attenuation and scattering. Most underwater image enhancement methods, first use linear transformations for color compensation and then enhance the image. We observed that linear transformation for color compensation is not suitable for certain images. For such images, a non-linear mapping is a better choice. Our paper introduces a unique underwater image restoration approach leveraging a streamlined convolutional neural network (CNN) for dynamic weight learning for linear and non-linear mapping. In the first phase, a classifier is applied that classifies the input images into Type-I or Type-II. In the second phase, depending on the classification, the Deep Line Model (DLM) for Type-I images or the Deep Curve Model (DCM) for Type-II images. For mapping an input image to an output image, DML creatively combines color compensation and contrast adjustment in a single step and uses deep lines for transformation, whereas DCM employs higher-order curves. Both models utilize lightweight neural networks that learn per-pixel dynamic weights based on the input image’s characteristics. Comprehensive evaluations on benchmark datasets using metrics like peak signal-to-noise ratio(PSNR) and root mean squares error (RMSE) affirm our method’s effectiveness in accurately restoring underwater images, outperforming existing techniques.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

The application of antimicrobials in aquaculture primarily aims to prevent and treat bacterial infections in fish. Inappropriate use of antimicrobials in fish farming may result in the emergence of zoonotic antibiotic-resistant bacteria and subsequent transmission of resistant strains to humans via food consumption. From recently, AMR emerged as a significant public health concern in the aquaculture ecosystem and fisheries. The aquatic environment serves as a potential reservoir for resistant bacteria, with aquaculture practices providing an ideal breeding ground for AMR due to the excessive use of antimicrobials to prevent and treat diseases. The mutual inter-connection of intensive fish farming systems with terrestrial environments, food processing industry and human population creates pathways for the transmission of resistant bacteria, exacerbating the problem further. One Health concept, which recognizes the interconnectedness of human, animal and environmental health, enables a holistic approach to address the challenges posed by AMR. By understanding the evolution of such approach, the future of aquaculture, being the important source of a global animal protein supply, can be safeguarded. Risk mitigation strategies for AMR should be based on One Health concept to contribute to sustainable aquaculture practices that protect human and animal health, ensure food safety and protection of environment.

This paper presents an on-device semi-supervised human activity detection system that can learn and predict human activity patterns in real time. The proposed semi-supervised learning (SSL) framework uses sparsely labelled user activity events acquired from Inertial Measurement Unit (IMU) sensors installed as wearable device. The objective is to learn classification of multiple classes of human activities in real-time. The proposed cluster-based learning model in this approach is trained with data from the same target user, thus preserving data privacy while providing personalized activity detection services. Two different cluster labelling strategies, namely, population-based, and distance-based, are employed to achieve the desired classification performance. A comparative study of these strategies has been presented in terms of classifiability and classification accuracies. The proposed system is shown to be computationally efficient, which is relevant in the context of limited computing resources on typical wearable devices. The trade-off between classification accuracy and computation complexity is analyzed for different algorithmic hyper-parameters and other system parameters. Extensive experimentation and simulation study have been conducted on a multi-user human activity data from the public do-main in order to validate the proposed learning paradigm.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and encompasses two main subtypes, Crohn’s disease (CD) and ulcerative colitis (UC). IBD is frequently accompanied by extraintestinal manifestations (EIMs), with axial and peripheral spondyloarthritis (SpA) being the most common. Enthesitis, an inflammation of the bone insertions of capsules, ligaments, and tendons, represents an initial lesion in SpA. However, enthesitis remains an underestimated and often obscured EIM. The early detection of subclinical enthesial involvement in IBD patients using ultrasound (US) could provide an opportunity for timely intervention. While previous meta-analyses have reported on the incidence and prevalence of SpA in IBD, specific attention to enthesitis has been lacking. Therefore, this narrative review aims to resume the current knowledge on existing IBD-SpA cohorts, focusing specifically on enthesitis.

Pore structure characterization and fractal analysis have great significance for understanding and evaluating tight limestone reservoirs. In this work, the pore structure of tight limestone is characterized combined with low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR), and the fractal dimension of tight limestone pore structure is discussed based on LTNA and NMR data. The results indicate that the pores of tight limestone have H3 and H4 types, the pore size distribution (PSD) of H3 type is a wave distribution ranging from 2 to 10 nm, and the PSD of H4 type is a unimodal distribution ranging from 2 to 10 nm. The transverse relaxation time (T2) spectrum of tight limestone shows single peak (DF), double peak (SF) and three peak (TF), and the T2 spectrums for micropores, mesopores and macropores range from 0.1 to 10 ms, from 10 to 100 ms, and greater than 100 ms, respectively. The LTNA fractal dimension of tight limestone (DL) ranges between 2.4446 and 2.7688, with an average of 2.5729, and the NMR fractal dimensions of micropores (DNMR1), mesopores (DNMR2) and macropores (DNMR3) are distributed between 0.3744 to 1.1293, 2.4263 to 2.9395 and 2.6582 to 2.9989, respectively. Moreover, there is no correlation between fractal dimension and permeability and porosity, a negative correlation between DL and average pore radius, a positive correlation between DL and specific surface area, and a positive correlation between DNMR2 and DNMR3 and micropore content, while DNMR2 and DNMR3 are negatively correlated with the content of mesopores and macropores.